FXYD3 (Mat-8; PLML) with two splice variants, one of 87 aas with 2 TMSs (an N-terminal leader sequence and a central very hydrophobic TMS) and the other of 116 aas and 2 TMSs (Bibert et al. 2006). Both FXYD3 variants co-immunoprecipitate with the Na,K-ATPase. They both associate stably with Na,K-ATPase isozymes but not with the H,K-ATPase or Ca-ATPase. The short human FXYD3 has 72% sequence identity with mouse FXYD3, whereas long human FXYD3 is identical to the short human FXYD3 but has a 26-amino acid insertion after the transmembrane domain. Short and long human FXYD3 RNAs and proteins are differentially expressed during differentiation with long FXYD3 being mainly expressed in nondifferentiated cells while short FXYD3 is expressed in differentiated cells (Bibert et al. 2006).

FXYD5 regulator of Na,K+-ATPase and ion channel activities of 178 aas and 1 C-terminal TMS. FXYD5 interacts directly with the Na+,K+-ATPase via their TMSs to affect the Vmax of the latter, and residues involved have been identified (Lubarski et al. 2007).